Trifluoroacetic acid → (R)-5-(1-Benzyl-1H-indol-3-yl)-4-(7-phenyl-heptanoylamino)-pent-2-enoic acid methyl ester

HRID 852850Notes

Reaction equation

HRID 852850 reaction equation
[C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13]([OH:15])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C.FC(F)(F)C(O)=O.[CH3:59][O:60][C:61](=[O:83])[CH:62]=[CH:63][CH:64]([NH2:82])[CH2:65][C:66]1[C:74]2[C:69](=[CH:70][CH:71]=[CH:72][CH:73]=2)[N:68]([CH2:75][C:76]2[CH:81]=[CH:80][CH:79]=[CH:78][CH:77]=2)[CH:67]=1>C1COCC1>[CH3:59][O:60][C:61](=[O:83])[CH:62]=[CH:63][C@H:64]([NH:82][C:13](=[O:15])[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[CH2:65][C:66]1[C:74]2[C:69](=[CH:70][CH:71]=[CH:72][CH:73]=2)[N:68]([CH2:75][C:76]2[CH:77]=[CH:78][CH:79]=[CH:80][CH:81]=2)[CH:67]=1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 81531Diisopropylethylamine2×HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 5209877-Phenyl heptanoic acidHCID 694139464-amino-5-(1-benzyl-1H-indol-3-yl)-pent-2-enoic acid methyl ester

Product 1

HCID 69415720(R)-5-(1-Benzyl-1H-indol-3-yl)-4-(7-phenyl-heptanoylamino)-pent-2-enoic acid methyl esterYield 85%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 7-phenylheptanoic acid (92 mg, 0.447 mmol), BOP (217 mg, 0.491 mmol) and DIPEA (69 mg, 93 μL, 0.535 mmol) in THF (2.5 mL) was stirred for 10 min. To this was added a solution of the trifluoroacetic acid salt of 4-amino-5-(1-benzyl-1H-indol-3-yl)-pent-2-enoic acid methyl ester (200 mg, 0.446 mmol) and DIPEA (173 mg, 233 μL, 1.34 mmol) in THF (2.5 mL). The mixture was stirred overnight at room temperature. The solvent was removed and the crude material subject to column chromatography (50% EtOAc/petroleum ether, Rf 0.66) to afford the title compound (197 mg, 85%). 1H NMR (CDCl3) δ 7.59 (1H, d, J=7.26 Hz), 6.94-7.28 (15H, m), 5.81 (1H, d, J=15.81 Hz), 5.48 (1H, d, J=8.34 Hz), 3.59 (2H, s), 5.05 (1H, m), 3.12 (1H, dd, J=6.42, 14.49 Hz), 3.04 (1H, dd, J=5.85, 14.49 Hz), 2.57 (2H, t, J=7.64 Hz), 2.07 (2H, t, J=7.67 Hz), 1.9-1.2 (8H, m). 13C NMR (CDCl3) δ 172.5, 166.5, 148.1, 142.6, 137.3, 136.6, 128.7, 128.4, 128.3, 128.2, 127.6, 126.9, 126.7, 125.6, 122.1, 120.8, 119.6, 118.8, 109.9, 109.4. 51.6, 49.9, 50.2, 36.7, 35.8, 31.2, 29.9, 29.0, 28.9, 25.4. ISMS: 523 (M+H).

Workup

  1. customThe solvent was removed

Sources & evidence

ORD record
ord-2272728b4aa54228b7b4117cc69ae7f2
Source dataset
uspto-grants-2007_08
Patent number
US07253194B2

Reaction notes

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